Laxative Treatment With Polyethylene Glycol Does Not Affect Lipid Absorption in Rats

Wulp, Mariette Y. M. van der; Cuperus, Frans J. C.; Stellaard, Frans; Dijk, Theo H. van; Dekker, Jan; Rings, Edmond H. H. M.; Groen, Albert K.; Verkade, Henkjan J.

doi:10.1097/mpg.0b013e3182555ba9

Cited by 7 publications

(6 citation statements)

References 36 publications

(64 reference statements)

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“…It was shown that intestinal transit time decreased by 20%, but there was no change in TC and TG levels in rats given PEG 4000 at a non-diarrheal dose. 28 We also detected lower serum glucose levels in HFD + PEG 3350 mice, which was close to but not statistically significant (p = 0.0571). Similarly, in humans, it was observed that there was no difference between PEG 3350 and placebo in terms of glucose levels in the treatment of functional constipation for 2 weeks.…”

Section: Discussionsupporting

confidence: 60%

A novel therapeutic approach to NASH: Both polyethylene glycol 3350 and lactulose reduce hepatic inflammation in C57BL/6J mice

et al. 2021

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Background. The gut-liver axis is one of the most emphasized topics in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). Intestinal microbiota dysbiosis has been shown to be a predictor of disease severity and progression to fatty liver disease. Therefore, research addressing gut-based therapies has become popular. Objectives.To investigate the effect of lactulose and polyethylene glycol 3350 (PEG 3350) in mice with induced obesity and NAFLD at a non-diarrheal dose. Materials and methods.Thirty-six C57BL/6J male mice were divided into 6 groups. The first 2 groups (n = 6 each) were used as an induced obesity model (group A) and NAFLD model (group B) for 8 weeks. The remaining 24 animals were categorized into control diet group, high-fat diet (HFD) group, HFD + lactulose group, and HFD + PEG 3350 group. Serum and liver tissue samples were obtained for biochemical and histopathological analyses, respectively.Results. The HFD + lactulose treatment group displayed a significant decrease in liver weight (1.3 (1.3-1.4) kg compared to 1.8 (1.6-1.9) kg) and NAFLD activity score (NAS) (1.5 (1.0-3.0) compared to 5.0 (4.0-5.0), respectively; p = 0.0043, p = 0.0021) when compared with the HFD group. However, a decrease in body weight (35.0 (34.6-36.0) kg compared to 40.9 (34.7-41.9) kg) and hepatosteatosis (HS) rate (33.3% compared to 100.0%) were not statistically significant (p = 0. 1796, p = 0.0606, respectively). The HFD + PEG 3350 treatment group showed a statistically significant decrease in body weight (32.4 (30.2-33.9) kg compared to 40.9 (34.7-41.9) kg), liver weight (1.5 (1.3-1.5) kg compared to 1.8 (1.6-1.9) kg), HS rate (16.7% compared to 100.0%) and NAS (0.5 (0.0-1.0) compared to 5.0 (4.0-5.0); p = 0.0086, p = 0.0086, p = 0.0151, and p = 0.0021, respectively) when compared with the HFD group.Conclusions. We demonstrated that non-diarrheal dose of lactulose and PEG 3350 reduced hepatic inflammation in mice with induced NAFLD. It was also observed that PEG 3350 decreased HS and body weight. We believe these mechanisms can be utilized as novel therapeutic approaches in NAFLD in prospective human studies.

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Section: Discussionsupporting

confidence: 60%

A novel therapeutic approach to NASH: Both polyethylene glycol 3350 and lactulose reduce hepatic inflammation in C57BL/6J mice

et al. 2021

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“…Laxative treatment shortens intestinal transit time and is able to alter microbiota and BA homeostasis. In rats, the commonly used laxative polyethylene glycol (PEG) decreased BA dehydroxylation, increasing the amount of primary BAs in the BA pool [119]. Whole body Cftr knockout mice display a severe intestinal phenotype and need to be kept either on a liquid diet or a solid diet in combination with laxative.…”

Section: Modulating Bile Acid Homeostasis To Improve Gastrointestinal Outcomes In Cystic Fibrosismentioning

confidence: 99%

Bile acid homeostasis in gastrointestinal and metabolic complications of cystic fibrosis

Peppel

Bodewes

Verkade

et al. 2019

Journal of Cystic Fibrosis

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With the improved treatment of the pulmonary complications of cystic fibrosis (CF), gastrointestinal problems have become more important in the morbidity in CF. A hallmark of the gastrointestinal phenotype of CF, apart from pancreatic insufficiency, is a disruption of bile acid homeostasis. Bile acid homeostasis is important for many gastrointestinal processes including fat absorption, inflammation, microbial composition, as well as regulation of whole body energy metabolism. This review describes the impairment of bile acid homeostasis in CF, its possible consequences for gastrointestinal and metabolic complications and its potential as a target for therapy.

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“…Fatty acids are not metabolized in the intestinal lumen, and we previously showed that the absorption and excretion of fatty acids is not changed by PEG (37), implying that fatty acids would not differentially influence fecal water cytotoxicity in PEG-treated rats. It should be realized that fecal water cytotoxicity has not been conclusively validated as a biomarker for colon cancer risk.…”

Section: Discussionmentioning

confidence: 99%

“…Food and fluid intake and body weight were measured daily. Some of the rat characteristics have been reported in our previous paper, which reported on the aspects of PEG treatment on fat and cholesterol absorption (37).…”

Section: Cholate Kinetic Studymentioning

confidence: 99%

Laxative treatment with polyethylene glycol decreases microbial primary bile salt dehydroxylation and lipid metabolism in the intestine of rats

Wulp

Derrien

Stellaard

et al. 2013

American Journal of Physiology-Gastrointestinal and Liver Physi

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van der Wulp MY, Derrien M, Stellaard F, Wolters H, Kleerebezem M, Dekker J, Rings EH, Groen AK, Verkade HJ. Laxative treatment with polyethylene glycol decreases microbial primary bile salt dehydroxylation and lipid metabolism in the intestine of rats. Am J Physiol Gastrointest Liver Physiol 305: G474 -G482, 2013. First published July 18, 2013; doi:10.1152/ajpgi.00375.2012.-Polyethylene glycol (PEG) is a frequently used osmotic laxative that accelerates gastrointestinal transit. It has remained unclear, however, whether PEG affects intestinal functions. We aimed to determine the effect of PEG treatment on intestinal sterol metabolism. Rats were treated with PEG in drinking water (7%) for 2 wk or left untreated (controls). We studied the enterohepatic circulation of the major bile salt (BS) cholate with a plasma stable isotope dilution technique and determined BS profiles and concentrations in bile, intestinal lumen contents, and feces. We determined the fecal excretion of cholesterol plus its intestinally formed metabolites. Finally, we determined the cytolytic activity of fecal water (a surrogate marker of colorectal cancer risk) and the amount and composition of fecal microbiota. Compared with control rats, PEG treatment increased the pool size (ϩ51%; P Ͻ 0.01) and decreased the fractional turnover of cholate (Ϫ32%; P Ͻ 0.01). PEG did not affect the cholate synthesis rate, corresponding with an unaffected fecal primary BS excretion. PEG reduced fecal excretion of secondary BS and of cholesterol metabolites (each P Ͻ 0.01). PEG decreased the cytolytic activity of fecal water [54 (46 -62) vs. 87 (85-92)% erythrocyte potassium release in PEG-treated and control rats, respectively; P Ͻ 0.01]. PEG treatment increased the contribution of Verrucomicrobia (P Ͻ 0.01) and decreased that of Firmicutes (P Ͻ 0.01) in fecal flora. We concluded that PEG treatment changes the intestinal bacterial composition, decreases the bacterial dehydroxylation of primary BS and the metabolism of cholesterol, and increases the pool size of the primary BS cholate in rats.cholate; enterohepatic circulation; bile salt; microbiota POLYETHYLENE GLYCOL (PEG) presently is one of the most widely prescribed laxatives. Long-term treatment with PEG is believed to be safe and highly effective (11,27). However, it is not known whether or not long-term PEG treatment affects specific intestinal metabolic functions. PEG may change the intestinal milieu by accelerating the passage of luminal contents and/or by increasing the luminal water content, possibly leading to a change in the intestinal microflora (10).We have previously shown that PEG treatment accelerates the transit through the small intestine as well as the whole gut in rats (10). PEG decreases fecal excretion of bile salts (BS) in rats (10). BS facilitate the solubilization of lipids (dietary fats, cholesterol, and fat-soluble vitamins) in the small intestine, which is required for efficient lipid absorption (41). It has recently become clear that BS not only are detergents necessary for lip...

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Laxative Treatment With Polyethylene Glycol Does Not Affect Lipid Absorption in Rats

Abstract: PEG does not affect lipid absorption nor steady-state plasma lipid levels in rats, although it accelerates the gastrointestinal transit.

Cited by 7 publications

References 36 publications

A novel therapeutic approach to NASH: Both polyethylene glycol 3350 and lactulose reduce hepatic inflammation in C57BL/6J mice

A novel therapeutic approach to NASH: Both polyethylene glycol 3350 and lactulose reduce hepatic inflammation in C57BL/6J mice

Bile acid homeostasis in gastrointestinal and metabolic complications of cystic fibrosis

Laxative treatment with polyethylene glycol decreases microbial primary bile salt dehydroxylation and lipid metabolism in the intestine of rats

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